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PMID:11849756

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Citation

Trotter, L, Panton, W, Hajimohamadreza, I, Petalidis, L, Ward, R, Fleming, Y, Armstrong, CG, Cohen, P, Karran, EH and Kinloch, RA (2002) Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons. Neurosci. Lett. 320:29-32

Abstract

A stress-activated protein kinase pathway comprising mitogen-activated protein kinase kinases (MKKs), c-Jun N-terminal kinase (JNK) and the transcription factor c-Jun is implicated in neuronal apoptosis. Using an immune-complex kinase assay, we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced apoptosis of rat cerebellar granule neurons (CGN). MKK7, but not MKK4, was activated within the first 4-6 h in four independent sets of 14-h CGN apoptosis time-courses. CEP-1347 (500 nM), an mixed-lineage kinase 3 inhibitor, prevented MKK7 activation and cell death following exposure of CGN cultures to LK-induced apoptosis. Western blot analysis revealed that levels of phosphorylated c-Jun were elevated between 30 min and 10 h of CGN apoptosis, temporally consistent with MKK7 activation. These data suggest that MKK7 is responsible for activating the JNK pathway during LK-induced CGN apoptosis.

Links

PubMed

Keywords

Animals; Animals, Newborn; Apoptosis/drug effects; Apoptosis/physiology; Cells, Cultured; Cerebellar Cortex/drug effects; Cerebellar Cortex/enzymology; MAP Kinase Kinase 7; MAP Kinase Signaling System/drug effects; MAP Kinase Signaling System/physiology; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors; Mitogen-Activated Protein Kinase Kinases/metabolism; Mitogen-Activated Protein Kinases/metabolism; Neurodegenerative Diseases/enzymology; Neurodegenerative Diseases/physiopathology; Neurons/drug effects; Neurons/enzymology; Oxidative Stress/drug effects; Oxidative Stress/physiology; Potassium Deficiency/enzymology; Potassium Deficiency/physiopathology; Rats; Up-Regulation/drug effects; Up-Regulation/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:MP2K7

involved_in

GO:0007254: JNK cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:MP2K7

enables

GO:0008545: JUN kinase kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:MK08

enables

GO:0004705: JUN kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

See also

References

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